Maintaining A Fixed Distance During Coating Of Drug Coated Balloon

ABSTRACT

A system and method for coating an expandable member of a medical device comprising a support structure to support the expandable member and a dispenser positioned with at least one outlet proximate a surface of an expandable member. A drive assembly establishes relative movement between the at least one outlet and the surface of the expandable member to apply fluid on the surface of the expandable member along a coating path. A guide maintains a substantially fixed distance between the at least one outlet and the surface of the expandable member during relative movement therebetween by displacing the expandable member relative to the at least one outlet.

CROSS-REFERENCE TO RELATED APPLICATION

This application claims priority to U.S. Provisional Application No.61/345,569 entitled “Maintaining a fixed distance during coating of drugcoated balloon,” filed May 17, 2010 which is incorporated herein byreference in its entirety.

BACKGROUND OF THE DISCLOSED SUBJECT MATTER

1. Field of the Disclosed Subject Matter

The presently disclosed subject matter is related to the delivery oftherapeutic agents from an interventional medical device. Moreparticularly, the presently disclosed subject matter relates to aninterventional device for delivery of therapeutic agents from anexpandable member, such as a balloon. The disclosed subject matter alsorelates to a method and apparatus for maintaining a fixed distancebetween a dispenser and the balloon surface during application of one ormore therapeutic agents onto the expandable member as well as theassembly of the medical device.

2. Description of Related Subject Matter

Atherosclerosis is a syndrome affecting arterial blood vessels. It ischaracterized by a chronic inflammatory response in the walls ofarteries, which is in large part due to the accumulation of lipid,macrophages, foam cells and the formation of plaque in the arterialwall. Atherosclerosis is commonly referred to as hardening of thearteries, although the pathophysiology of the disease manifests itselfwith several different types lesions ranging from fibrotic to lipidladen to calcific. Angioplasty is a vascular interventional techniqueinvolving mechanically widening an obstructed blood vessel, typicallycaused by atherosclerosis.

During angioplasty, a catheter having a folded balloon is inserted intothe vasculature of the patient and is passed to the narrowed location ofthe blood vessel at which point the balloon is inflated to the desiredsize by fluid pressure. Percutaneous coronary intervention (PCI),commonly known as coronary angioplasty, is a therapeutic procedure totreat the stenotic regions in the coronary arteries of the heart, oftenfound in coronary heart disease. In contrast, peripheral angioplasty,commonly known as percutaneous transluminal angioplasty (PTA), generallyrefers to the use of mechanical widening of blood vessels other than thecoronary arteries. PTA is most commonly used to treat narrowing of theleg arteries, especially, the iliac, external iliac, superficial femoraland popliteal arteries. PTA can also treat narrowing of carotid andrenal arteries, veins, and other blood vessels.

Although the blood vessel is often successfully widened by angioplasty,sometimes the treated region of the blood vessel undergoes vasospasm, orabrupt closure after balloon inflation or dilatation, causing the bloodvessel to collapse after the balloon is deflated or shortly thereafter.One solution to such collapse is stenting the blood vessel to preventcollapse. Dissection, or perforation, of the blood vessel is anothercomplication of angioplasty that can be improved by stenting. A stent isa device, typically a metal tube or scaffold that is inserted into theblood vessel after, or concurrently with angioplasty, to hold the bloodvessel open.

While the advent of stents eliminated many of the complications ofabrupt vessel closure after angioplasty procedures, within about sixmonths of stenting a re-narrowing of the blood vessel can form, acondition known as restenosis. Restenosis was discovered to be aresponse to the injury of the angioplasty procedure and is characterizedby a growth of smooth muscle cells and extracellular matrix—analogous toa scar forming over an injury. To address this condition, drug elutingstents were developed to reduce the reoccurrence of blood vesselnarrowing after stent implantation. A drug eluting stent is a stent thathas been coated with a drug, often in a polymeric carrier, that is knownto interfere with the process of re-narrowing of the blood vessel(restenosis). Examples of various known drug eluting stents aredisclosed in U.S. Pat. Nos. 5,649,977; 5,464,650; 5,591,227, 7,378,105;7,445,792; 7,335,227, each of which are hereby incorporated by referencein their entirety. However, a drawback of drug eluting stents is acondition known as late stent thrombosis. This is an event where a bloodclot forms inside the stent, which can occlude blood flow.

Drug coated balloons are believed to be a viable alternative to drugeluting stents in the treatment of atherosclerotic lesions. In a studywhich evaluated restenosis, and the rate of major adverse cardiac eventssuch as heart attack, bypass, repeat stenosis, or death in patientstreated with drug coated balloons and drug eluting stents, the patientstreated with drug coated balloons experienced only 3.7 percentrestenosis and 4.8% MACE (major adverse coronary events) as compared topatients treated with drug eluting stents, in which restenosis was 20.8percent and 22.0 percent MACE rate. (See, PEPCAD II study, Rotenburg,Germany)

However, drug coated balloons present certain unique challenges. Forexample, the drug carried by the balloon needs to remain on the balloonduring delivery to the lesion site, and released from the balloonsurface to the blood vessel wall when the balloon is expanded inside theblood vessel. For coronary procedures, the balloon is typically inflatedfor less than one minute, typically about thirty seconds. The ballooninflation time may be longer for a peripheral procedure, howevertypically even for peripheral procedures the balloon is expanded forless than 5 minutes. Due to the short duration of contact between thedrug coated balloon surface and the blood vessel wall, the ballooncoating must exhibit efficient therapeutic agent transfer and/orefficient drug release during inflation. Thus, there are challengesspecific to drug delivery via a drug coated or drug eluting balloon thatare not present with a drug eluting stent.

Furthermore, conventional techniques for applying a coating, such as atherapeutic agent, may not be desirable for coating balloons, or otherexpandable members of medical devices. Such convention techniquesinclude spraying (air-atomization, ultrasonic, electrostatic, etc.),dip-coating, spin-coating, vapor deposition, roll coating, micro-dropletcoating, etc. Balloons present a cylindrical surface to be coated whereit is desired to uniformly coat only the working length of the balloonand no other portion of the balloon or catheter. Techniques such asspraying are needed to coat the fine geometry of stents without webbingbut are very inefficient, with a low coating efficiency. However,balloons do not have this requirement and the low drug utilizationefficiency is undesirable, particularly for large peripheral balloons.Many of these conventional techniques do not provide sufficient coatinguniformity or edge control. For example, it is often desirable to applythe coating to balloon surface when the balloon is at least partiallyinflated, however balloons which are not cylindrical in shape whenexpanded, such as peripheral balloons, often warp or bow upon inflation.Consequently, a non-uniform coating is applied to the balloon surfacethereby leading to a non-uniform drug distribution with even thepotential for bare spot with no coating. In addition, this compromisesthe efficiency in the coating process, can degrade the efficacy of thetherapeutic agent, and an inappropriate coating process can lead tofurther distorting or bowing of the balloon.

Thus there remains a need, and an aim of the disclosed subject matter isdirected towards, maintaining a fixed distance between the coatingdispenser and the surface of the balloon during the application of oneor more therapeutic agents to the surface of an expandable member of amedical device.

SUMMARY OF THE DISCLOSED SUBJECT MATTER

The purpose and advantages of the disclosed subject matter will be setforth in and are apparent from the description that follows, as well aswill be learned by practice of the disclosed subject matter. Additionaladvantages of the disclosed subject matter will be realized and attainedby the methods and systems particularly pointed out in the writtendescription and claims hereof, as well as from the appended drawings.

To achieve these and other advantages and in accordance with the purposeof the disclosed subject matter, as embodied and broadly described, thedisclosed subject matter includes a system and method of coating anexpandable member of a medical device. The system and correspondingmethod comprises providing an applicator in fluid communication with afluid source, with the applicator having at least one outlet forapplying fluid therefrom, and positioning the applicator proximate asurface of an expandable member. Relative movement is establishedbetween the at least one outlet and the surface of the expandable memberalong a coating path while maintaining a substantially fixed distancebetween the at least one outlet and the surface of the expandable memberduring relative movement therebetween. From the fixed distance, fluid isapplied from the at least one outlet to form a controlled coating offluid on the surface of the expandable member along the coating path.

The substantially fixed distance between the expandable member and theat least one outlet is maintained by displacing the expandable memberrelative to the at least one outlet. For example, maintaining thesubstantially fixed distance can include constraining displacement ofthe expandable member during relative movement between the at least oneoutlet and the surface of the expandable member. Constrainingdisplacement can include providing a guide to constrain displacement ofthe expandable member in at least one direction during relative movementbetween the at least one outlet and the surface of the expandablemember.

In some embodiments, the guide includes at least one constraining memberhaving at least one discrete point of a contact with the surface of theexpandable member. Alternatively, the guide can include at least twoconstraining members contacting generally opposing sides of theexpandable member. Alternatively, the guide is a generally U-shapedmember having three discrete points of contact with the surface of theexpandable member. Alternatively, the guide substantially surrounds aperimeter of the expandable member.

The amount of displacement can vary along a length of the expandablemember. For example, the amount of displacement can increase along alength of the expandable member. The expandable member can at least bepartially expanded prior to dispensing fluid to the surface of theexpandable member.

It is to be understood that both the foregoing general description andthe following detailed description are exemplary and are intended toprovide further explanation of the disclosed subject matter claimed.

The accompanying drawings, which are incorporated in and constitute partof this specification, are included to illustrate and provide a furtherunderstanding of the method and system of the disclosed subject matter.Together with the description, the drawings serve to explain theprinciples of the disclosed subject matter.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic side view representative balloon catheter inaccordance with the disclosed subject matter.

FIG. 1A is a cross-sectional view taken along lines A-A in FIG. 1.

FIG. 1B is a cross-sectional view taken along lines B-B in FIG. 1.

FIG. 2 is a schematic representation of a direct fluid coating processand system.

FIGS. 3A-D are schematic views of various embodiments of a guide tocontrain an expandable member in accordance with the disclosed subjectmatter.

FIGS. 4-6 are schematic views of alternative embodiments of a guide fordisplacing an expandable member in accordance with the disclosed subjectmatter.

FIGS. 7A-H are schematic views of alternative embodiments of a guide todisplace an expandable member in accordance with the disclosed subjectmatter.

FIG. 8 is a schematic cross-sectional view of the guide embodiment shownin FIG. 7H.

FIG. 9 is a schematic front view of a guide in accordance with an aspectof the disclosed subject matter.

FIG. 10 is a schematic view of alternative embodiment of a guide inaccordance with an aspect of the disclosed subject matter.

FIG. 11 is a schematic cross-sectional view of a support assembly forsupporting the shaft of the catheter during a coating process.

DETAILED DESCRIPTION

Reference will now be made in detail to the embodiments of the disclosedsubject matter, an example of which is illustrated in the accompanyingdrawings. The method and corresponding steps of the disclosed subjectmatter will be described in conjunction with the detailed description ofthe system.

The methods and systems presented herein can be used for applying one ormore coatings to a medical device. The disclosed subject matter isparticularly suited for applying a uniform coating of therapeuticagents, and other fluid compounds, to select portions of an expandablemember. While the disclosed subject matter references application of afluid to an expandable member, it is to be understood that the methodsand systems disclosed herein can also be employed to apply therapeutic,polymeric, or matrix coatings to various surfaces of medical devices, asso desired.

The disclosed subject matter provides a method, and correspondingsystem, to coat an expandable member, or select portions thereof, by avariety of application processes while maintaining a substantially fixeddistance between the outlet of the applicator and the surface of theexpandable member. In one embodiment, the expandable member can becoated by a direct fluid coating application process; howeveralternative coating methods can be employed in accordance with thedisclosed subject matter. The direct fluid coating applies a coatingwithout atomization, or the formation of droplets, of the coating fluid.Additionally, the direct fluid coating process improves the efficiencyof the dispensing of a coating solution, which can be controlled basedon the volume of coating solution dispensed, rather than via a weightbased control. Indeed, the direct fluid coating process provides asystem and method for dispensing of a coating solution which can achieve95.0% or greater transfer efficiency, i.e., 95.0% of the coatingsolution dispensed is applied to the expandable member.

In accordance with the disclosed subject matter, a system andcorresponding method of coating an expandable member of a medical devicecomprises providing an applicator in fluid communication with a fluidsource, with the applicator having at least one outlet for applyingfluid therefrom, and positioning the applicator proximate a surface ofan expandable member. Relative movement is established between the atleast one outlet and the surface of the expandable member along acoating path while maintaining a substantially fixed distance betweenthe at least one outlet and the surface of the expandable member duringrelative movement therebetween. From the fixed distance, fluid isapplied from the at least one outlet to form a coating of fluid on thesurface of the expandable member along the coating path. For embodimentsutilizing the direct fluid coating process, fluid is dispensed from thedispenser to form a substantially continuous bead of fluid between theoutlet and the surface of the expandable member along the coating path.

For purpose of explanation and illustration, and not limitation, anembodiment of a medical device having an expandable member is shownschematically in FIGS. 1 and 1A. Particularly, and as illustrated, themedical device embodied herein is a balloon catheter 10, which includesan elongated catheter shaft 12 having a proximal end and having a distalend and an expandable member 30 located proximate the distal end of thecatheter shaft. The expandable member, or balloon as depicted herein,has an outer surface and an inner surface disposed at the distal endportion of the catheter shaft. In accordance with the disclosed subjectmatter, a coating is applied to at least a portion of the outer surfaceof the balloon.

The elongated catheter shaft 12 comprises an outer tubular member 14 andan inner tubular member 16. The outer tubular member 14 defines aninflation lumen 20 disposed between the proximal end portion and thedistal end portion of the catheter shaft 12. Specifically, asillustrated in FIG. 1A, the coaxial relationship of this representativeembodiment defines an annular inflation lumen 20 between the innertubular member 16 and the outer tubular member 14. The expandable member30 is in fluid communication with the inflation lumen 20. The inflationlumen can supply an inflation medium under positive pressure and canwithdraw the inflation medium, i.e. provide negative pressure, from theexpandable member. The expandable member 30 can thus be inflated anddeflated. The elongated catheter is sized and configured for deliverythrough a tortuous anatomy, and can further include a guidewire lumen 22that permits it to be delivered over a guidewire 18. As illustrated inFIG. 1A, the inner tubular member 16 defines the guidewire lumen 22 forthe guidewire 18. Although FIGS. 1 and 1 b illustrate the guidewirelumen as having an over-the-wire (OTW) construction, the guidewire lumencan be configured as a rapid-exchange (RX) construction, as is wellknown in the art.

A wide variety of balloon catheters and balloon constructs are known andsuitable for use in accordance with the disclosed subject matter. Forexample, the expandable member can be made from polymeric material suchas compliant, non-compliant or semi-compliant polymeric material orpolymeric blends. Examples of such suitable materials include, but arenot limited to, nylon 12, nylon 11, nylon 9, nylon 6, nylon 6/12, nylon6/11, nylon 6/9, and nylon 6/6, polyurethane, silicone-polyurethane,polyesters, polyester copolymers, and polyethylene. Examples of otherballoon and catheter embodiments which can be employed in accordancewith the disclosed subject matter include U.S. Pat. Nos. 4,748,982;5,496,346; 5,626,600; 5,300,085, 6,406,457 and application Ser. Nos.12/371,426; 11/539,944; 12/371,422, each of which is hereby incorporatedby reference in their entirety.

In one embodiment, the coating is applied to the expandable member ofthe fully assembled medical device. As described above with reference toFIGS. 1, 1A-B, medical devices such as the catheter 10 include aplurality of components which are typically manufactured as separatediscrete components and thereafter assembled together. Applying acoating to the expandable member at an upstream stage of an assemblyline requires extensive measures to minimize or prevent the coating frombeing exposed to various equipment and processes during the downstreamportion of the assembly line. Such exposure can render the coating proneto damage and/or contamination during final assembly of the catheter,and can result in scrapping of the entire catheter. In order to avoidsuch exposure and damage to the coating in conventional catheterassembly lines additional equipment including monitoring and safetycontrols would be required. Accordingly, applying the coating to theexpandable member of a fully assembled catheter avoids the unnecessarycomplexity, and excessive costs associated with such a modified assemblyline.

In accordance with the disclosed subject matter, any of a variety offluid compositions can be applied to the expandable member. For example,the fluid can include a therapeutic agent for treatment of a diseasestate. Examples of suitable therapeutic agents includeanti-proliferative, anti-inflammatory, antineoplastic, antiplatelet,anti-coagulant, anti-fibrin, antithrombotic, antimitotic, antibiotic,antiallergic and antioxidant compounds. Such therapeutic agents can be,again without limitation, a synthetic inorganic or organic compound, aprotein, a peptide, a polysaccharides and other sugars, a lipid, DNA andRNA nucleic acid sequences, an antisense oligonucleotide, an antibodies,a receptor ligands, an enzyme, an adhesion peptide, a blood clot agentincluding streptokinase and tissue plasminogen activator, an antigen, ahormone, a growth factor, a ribozyme, and a retroviral vector. However,the therapeutic agents include, cytostatic drug. The term “cytostatic”as used herein means a drug that mitigates cell proliferation but allowscell migration. These cytostatic drugs, include for the purpose ofillustration and without limitation, macrolide antibiotics, rapamycin,everolimus, zotaroliumus, biolimus, temsirolimus, deforolimus,novolimus, myolimus, structural derivatives and functional analogues ofrapamycin, structural derivatives and functional analogues ofeverolimus, structural derivatives and functional analogues ofzotarolimus and any marcrolide immunosuppressive drugs. The term“cytotoxic” as used herein means a drug used to inhibit cell growth,such as chemotherapeutic drugs. Some non-limiting examples of cytotoxicdrugs include vincristine, actinomycin, cisplatin, taxanes, paclitaxel,and protaxel.

Additionally, or alternatively, the fluid can include other compounds oradditives, such as polymers, binding agents, plasticizers, solvents,surfactants, additives, chelators, fillers, and the like. Examples ofpossible compounds include zotarolimus, polyvinylpyrrolidone andglycerol. In one embodiment the therapeutic agent can be provided inliquid form or dissolved in a suitable solvent. In another embodiment,the therapeutic agent is provided as a particulate and mixed in asuitable carrier for application as a fluid.

In accordance with an aspect of the disclosed subject matter, a varietyof techniques for applying a coating of therapeutic agent can beemployed, such as direct fluid coating, spraying (air-atomization,ultrasonic, electrostatic, etc.), jetting, vapor deposition,micro-droplet coating, etc. For example, the dispenser apparatus andcorresponding coating techniques disclosed in U.S. Pat. No. 7,455,876and U.S. Patent Application Publication No. 2010/0055294, the entiretyof each is hereby incorporated by reference, can be employed inaccordance with the disclosed subject matter.

An embodiment of the coating process and system of the disclosed subjectmatter is illustrated in FIG. 2 for purpose of explanation and notlimitation. The dispenser depicted herein is shown as a pipet or tube100 having an outlet positioned proximate expandable member 30 such thatthe fluid dispensed from the pipet is in continuous fluid contact withthe expandable member 30 without atomization of the coating solution. Asthe coating solution is delivered from a fluid source, e.g. reservoir(not shown), through the dispenser outlet, a continuous fluid medium orbead 200 of solution directly contacts the surface of the expandablemember. FIG. 2 depicts the pipet 100 generally at a right angle to theballoon surface. However, alternative alignments and orientations can beused as desired or needed for the type and dimensions of expandablemembers.

A positive pressure is applied to assist with dispensing fluid from theoutlet. In addition, due to capillary action, the surface tension pullsthe bead of coating solution 200 onto the surface of the expandablemember. Furthermore, the outlet can be heated prior to and/or during thedispensing of the coating solution. The heating of the dispenser canreduce the viscosity of the coating solution and therefore acceleratethe coating process as well as reduce the potential for clogging oroccluding of the dispenser outlet 102. FIG. 2 depicts the outletgenerally at a right angle to the balloon surface.

Coating process and systems of the disclosed subject matter can beperformed with the expandable member in a fully or partially inflatedcondition, or even in a deflated condition. When deflated, theexpandable member can be pleated, folded, wrinkled or pressed. In theembodiment illustrated in FIG. 2, the expandable member is fullyinflated to allow coating of all or select portions of the outersurface. Additionally, the temperature of expansion medium, or theexpandable member itself, can be controlled to further manipulate thecontour of the expandable member.

As the fluid is delivered from the dispenser, relative movement isestablished between the dispenser 100 and the expandable member 30 toeffect a continuous, or patterned coating path as desired. For example,and as depicted in FIG. 2, the coating path can define a continuousspiral or helical pattern along the outer surface of the expandablemember. Alternatively, coating paths can be established such as discretecircumferential rings, discrete lines extending along the expandablemembers longitudinal axis, and combinations thereof. Hence, the relativemovement can include rotation, translation, or combinations thereof, ofeither, or both, the expandable member 30 and the dispenser 100.

For example, the expandable member 30 can be rotated about its centralaxis, as shown by arrows A in FIG. 2, and simultaneously translatedalong the central axis, as shown by arrow B in FIG. 2. Additionally, oralternatively the expandable member 30 can rotate relative a first axis,and the dispenser 100 translate relative a second axis, e.g., to definea helical coating path. Accordingly, any number of coating paths can beselected and provided on the expandable member. The various movementsdescribed herein can be performed simultaneously, sequentially,continuously or intermittently, as so desired.

Movement of the medical device and/or the outlet of the dispenser isaccomplished by providing a support assembly. The support assembly canmaintain the position of one element, e.g. the dispenser, while allowingmovement of the other element, e.g., the medical device. Alternatively,the support assembly can allow movement of both elements. Movement canbe performed manually, or by providing a drive assembly with suitabledrive source, such as a motor or the like, and appropriate controller asknow in the art.

Simultaneous with the relative movement, the fluid is dispensed from theoutlet to form a continuous bead between the outlet and the surface ofthe expandable member along the coating path. Generally, it has beendetermined that the formation and maintenance of the continuous bead offluid will be a function of the fluid density, and average velocity ofthe fluid from the outlet. In one embodiment, the Reynolds number, i.e.ratio of momentum or inertial force to viscosity, for the flow out ofthe outlet is less than 2300 such that the flow remains substantiallylaminar. The Reynolds number being defined by the equation Re=(ρ*v*l)/μ,wherein “1” is a dimension of the outlet.

The desired portions of the expandable member can be coated with asingle pass or cycle of relative movement between the expandable memberand dispenser. Alternatively, a plurality of passes or cycles of coatingoperation discussed above can be performed. Such multiple passes orcycles allows for further variation in the coating properties along theexpandable member length. For example, one portion of the expandablemember can be coated with a different number of coating layers of fluidthan another portion of the expandable member thereby creating agradient of the coating solution on the expandable member. Further, themethods and apparatus of the disclosed subject matter can be employed toapply layers of different coating compositions to the expandable member.For example, therapeutic-free primers, concentrated therapeutic layers,and drug-excipient layers can be applied. As discussed above, variedcoating properties allow for greater flexibility and customization ofthe catheter to provide a greater range of applications and ability tomeet patient needs.

In accordance with another aspect of the disclosed subject matter, adrying apparatus can be employed to accelerate the coating process. Asshown in FIG. 2, a dryer 300 can be positioned downstream of thedispenser to apply heat, forced gas, cooled gas, vacuum, infra-redenergy, microwave energy, or a combination thereof to the surface of theexpandable member. The drying nozzle may also be collinear or coaxialwith the dispenser by either circumscribing it or by have the dispensersurround it as with an annular opening. In some embodiments, a dryingoperation can be conducted between successive coating passes or cycles.Additionally, or alternatively, the drying operation can be conductedconcurrently with a coating pass or cycle, as depicted in FIG. 2.Similar to the dispenser 100 discussed above, the drying apparatus 300can be oriented at any angle between 0°-90° with respect to theexpandable member, and be configured for relative movement.

While the dispenser of the embodiment illustrated in FIG. 2 depicts adispenser configured as a pipet, additional or alternative dispenserscan be employed. Some examples of such dispensers include flexibletubing, coaxial tubing, hypotubes, dies, ball-bearing dispense tubing,syringe, needles, brushes, sponges, cones and foam applicators.Furthermore, FIG. 2 depicts a dispenser having a single outlet 102perpendicular to the expandable member though alternative angles between0°-90° can be employed. Also, the use of a plurality of outlets can beemployed. Each outlet can be oriented perpendicular, disposed adjacenteach other along the axis of the expandable member, and/or spacedcircumferentially about the expandable member.

In this regard, a plurality of reservoirs containing distinct coatingsolutions can be provided with each dispenser in fluid communicationwith a separate reservoir. As with the outlet of FIG. 2, the dispenserscan be positioned at various locations and orientations relative to theexpandable member. Additionally, the expandable member 30 can beoriented in a generally horizontal position, as shown in FIG. 2,vertically, or at or at any angle between 0°-90°, if desired. Orientingthe expandable member in a vertical configuration can be advantageous inlarger size expandable members, e.g. peripheral balloons, since thegravitational force acts parallel the expandable member's longitudinalaxis thereby preventing deformation such as arching or bowing of theexpandable member and associated catheter shaft, which the expandablemember can be susceptible to when in the horizontal position.

As previously noted, and in accordance with the disclosed subjectmatter, the dispenser is maintained at a predetermined or fixed distancefrom the expandable member surface. Maintaining a fixed distance betweenthe dispenser outlet and the expandable member, in combination withrotation and translation as discussed above, provides greater controlover the coating pattern to be applied to the expandable member surface.Such control can be advantageous by providing a consistent and uniformdosage of the therapeutic agent along the surface of the expandablemember, resulting in a balanced expandable member.

Additionally, maintaining a fixed distance between the dispenser outletand the expandable member surface reduces the amount of waste or excesscoating which is not retained on the expandable member. For example,with spray coating techniques, the amount of waste or excess coatinggenerally increases with the distance between the outlet(s) and thesurface of the expandable member. For example, with direct coatingtechniques, discrete droplets of fluid could form if the distancebetween the outlet and the surface of the expandable member were toogreat. Conversely, if the distance between the dispenser outlet and theexpandable member surface were too small, undesired or accidentalcontact between the dispenser outlet and expandable member surface canoccur resulting in tearing or scratching of the expandable membersurface or abrasion to the coating applied to the expandable member. Thedistance between the outlet and the surface of the expandable member candepend upon a number of variables, including viscosity of the fluid,surface tension of the fluid, pump rate of the fluid, diameter of thedispenser exit orifice, volatility of the solvents in the fluid, speedat which the fluid is dispensed and/or size of the outlet opening. Forexample, when using a pipet type dispenser, the distance between theoutlet and the surface generally should be less than 40 times thesmallest cross dimension of the outlet.

The fixed distance between the outlet and the surface of the expandablemember can be monitored and maintained in a number of ways in accordancewith the disclosed subject matter. For example, the fixed distance canbe maintained between the dispenser outlet and the expandable membersurface by constraining displacement of the expandable member via aguide member during relative movement. Constraining displacementprovided by the guide ensures that the surface of the expandable memberexiting the guide is accurately positioned in a predetermined location.In other words, as a bowed or otherwise non-cylindrical expandablemember enters the guide, the surface contour of the expandable member isforced to comply with the geometry of the guide, resulting in apredictable and constant location of the expandable member upon exitingthe guide. Accordingly, the expandable member can be maintained in anintentionally bowed or deformed shape during a coating cycle.

Based on this known or predetermined location of the expandable memberexiting the guide, the applicator (e.g. spray nozzle, pipet, etc.) isdisposed a predetermined distance from the guide member such that acontrolled and uniform coating is applied over the desired length of theexpandable member. Further, the predetermined distance between thedispensing means and the guide can be adjusted as so desired toaccommodate various sizes of expandable members, as well as varioussizes or types of dispensers.

The guide can be positioned proximate the dispenser outlet to avoidcontact with the newly dispensed coating from the outlet. For example,the guide can be positioned laterally adjacent to the dispenser outlet,or distal the dispenser outlet provided the guide does not lie in a pathin which it might encounter a fresh or wet coating. The guide can becoated with or fabricated of a durable, low friction material such asthermoplastic and thermoset polymers. Examples of which include, forpurpose of illustration and not limitation, polyethylene, polypropylene,polytetraflouroethylene (PTFE), fluorinated ethylene propylene (FEP),poly(vinylidene fluoride) (PVDF), poly(tetraflouroethylene-co-ethylene),and nylons.

In the embodiments illustrated in FIGS. 3A-D, a guide 500 serves as aconstraining member and is configured as a collar which circumscribesand/or houses the expandable member. The guide 500 is formed having alength and material of sufficient rigidity to maintain the expandablemember in a fixed geometry. The guide 500 is capable of moving, e.g.translating along the expandable member's longitudinal axis. Forexample, the guide 500 can be mounted above the expandable member, asshown in FIG. 3A, or below the expandable member as shown in FIG. 3B forsuch movement. The guide 500 is rigidly attached to a mounting member600 which is configured to translate along rail 602. Rail 602 isarranged in a parallel manner to the longitudinal axis of the expandablemember such that the guide 500 can translate relative to the expandablemember during the coating process. Alternatively, the guide 500 can be asingle-piece member with a fixed size in which the expandable member isinserted inside or through the guide prior to application of thecoating. Additionally, or alternatively, the guide 500, and dispenser100, can be fixed in place and the expandable member translated-rotatedrelative to them.

The embodiments of FIGS. 3A-B depict a guide 500 in the form of acontinuous collar which circumscribes a portion of the expandablemember. FIG. 3C depicts an embodiment of the guide 500 in the form of aspring-like structure. Such a spring-like or helical support structureis advantageous in that it provides sufficient rigidity and support tothe expandable member, while reducing the surface area of the expandablemember in contact with the guide, thereby reducing friction and the riskof damage to the coating layer or expandable member surface. As shown inFIG. 3D, which depicts a cross-sectional view of a single spiral elementof the guide of FIG. 3C, the amount of surface area of the expandablemember in contact with the guide is localized to a discrete point ofcontact 510.

In an alternative embodiment, the guide depicted in FIG. 4 includes aplurality of pins 502, 504 disposed on opposite sides the expandablemember. The pins 502, 504 can be oriented at any angle less than 90degrees depending on the dimensions of the expandable member and can bemounted to a fixture as stationary members, or moved relative to theexpandable member. Additionally, the pins 502, 504 are provided with afixed spacing therebetween thus ensuring accurate positioning of theexpandable member exiting the pins 502, 504 irrespective of any bowingor otherwise asymmetrical shape of the expandable member. Similar to theembodiment of FIG. 3C, the discrete surface contact established by thepins 502, 504 provides sufficient rigidity and support to the expandablemember, while reducing the surface area of the expandable member incontact with the guide, thereby reducing friction and the risk of damageto the coating layer or expandable member surface. As an alternative tothe pins 502, 504 as illustrated in FIG. 5, elongated plates can beutilized in a similar fashion such that the plates are diametricallyopposed on opposite sides of the expandable member and constrain anydisplacement of the expandable member proximate the plates. Each platecan be configured to engage the expandable member tangentially at adiscrete line of contact. In either embodiment, the pins or platesprovide discrete points of contact. Furthermore, the pins or plates canbe repositioned to accommodate expandable members of varying sizes. Ifso desired, a lubricant can be applied to the guide to inhibit orprevent the generation of frictional forces during operation.

Alternatively, or additionally, stabilizing shoulder cones, asillustrated in FIG. 6, can be positioned in contact with the shouldersof the expandable member, defined as the transition region between theworking length and tapered sections of the expandable member. Further,the guide can be configured with an inner diameter which is smaller thanthe outer diameter of the expandable member. Upon insertion of theexpandable member 30 within the guide 500, the expandable member wouldbe slightly deformed to counteract any bowing tendencies of theexpandable member. Further, the guide 500 can be configured as tubing orchambers, which are inflatable/deflatable such that dynamicpressurization of the collars 500 could occur to offset any bowingeffect. For example a proximal collar 503 could be inflated to adifferent pressure than distal collar 505.

In accordance with another aspect of the disclosed subject matter, theguide can be provided in the form of a channel which captures orreceives a portion of the expandable member. With reference to FIGS.7A-7H, for purpose of illustration and not limitation, the channel canbe provided with a variety of shapes and dimensions. For example, FIG.7A depicts a guide or channel having a partial cylindrical shape with aninner diameter generally corresponding to the diameter of the inflatedexpandable member. FIGS. 7B-F depict various guides of differentlengths, each with a generally rectangular cross-section to define threelocations of contact with the expandable member. FIGS. 7G-H each depicta guide having a top plate to contact the expandable member along adiscrete line, and depending legs to engage the expandable member atdiscrete points of contact.

In the embodiment of FIG. 7H, the guide can be configured as a yoke todepresses individual or multiple sections of the surface of theexpandable member while the fluid is dispensed onto the surface of theexpandable member. In this manner, as the relative movement isestablished between the dispenser outlet and the expandable member, thearea of the expandable member proximate the guide remains at a fixed andpredictable position during the coating cycle.

According to another aspect of the disclosed subject matter, the guidecan include a plurality of constraining members of various dimensionsand sizes that can be arranged in series. For example, a series ofprogressively narrower guides can be arranged to receive and constrainor deform the expandable member. Furthermore, it is to be understoodthat the dimensions and size of the guides can be varied to accommodatea variety of expandable members. The guides of the disclosed subjectmatter can be formed from any suitable material, non-limiting examplesof which include PTFE, poly (etheretherketone) (PEEK), FEP, PVDF,aluminum and stainless steel.

The guide 500 can be formed in a variety of dimensions selected to suitthe particular application and dimensions of the expandable member. Asdiscussed above, a series of guides of varying dimensions can be alignedto progressively constrain the expandable member. For example, and withreference to the guide of FIG. 8, guides for use with expandable membersof 5.0 mm and 6.0 mm can be configured with the dimensions provided inTable 1 below.

Dimension Guide 1 Guide 2 Guide 3 Guide 4 x (mm) 5.15 +/− 0.05 6.15 +/−0.05 5.15 +/− 0.05 6.15 +/− 0.05 y (mm)  4.9 +/− 0.05  5.9 +/− 0.05  4.9+/− 0.05  5.9 +/− 0.05 z (mm) 7.5 +/− 0.1 7.5 +/− 0.1 7.5 +/− 0.1 7.5+/− 0.1 length (x¹) (mm) 10 10 20 20

Alternatively, and as shown in FIG. 9, the guide can be constructed frompins or rods rather than plates or collars, to minimize the contactbetween the guide 500 and the expandable member 30. Similarly, thedepending legs of the guide in FIGS. 7G-H, likewise can be formed asrods or pins. This configuration provides three discrete points ofcontact between the expandable member and guide, thereby minimizing therisk of damage to the coating layer or expandable member surface. Thisminimal contact between the expandable member and the guide isadvantageous in reducing the forces required to establish the relativemovement between the expandable member and the dispenser outlet. Forpurpose of illustration, an expandable member exhibiting a 2 mm bow,which is defined as the amount of deflection from the longitudinal axisof the expandable member, was constrained within the guide of FIG. 7H toreduce the bow to 0.5 mm.

In an alternative embodiment, the guide can be configured as a weightedanchor having two wire-like members 541, 542 draped over and in contactwith the expandable member 30, as shown in FIG. 10. The wire-likemembers can be made of teflon, delrin, PPE, or any other material havinga suitable coefficient of friction to avoid damaging the expandablemember, or coating disposed thereon. The weight of the anchor portion,as well as the dimensions and cross-sectional shape of the wire-likemembers 541, 542 can vary depending on the properties of the expandablemember, and the desired amount of deformation desired.

As discussed above, the coating method and system of the disclosedsubject matter can be performed on a previously assembled medicaldevice, e.g. balloon catheters. Often the force required to rotate orotherwise move the expandable member is applied to a location, and/orcomponent, proximal of the expandable member. Therefore, significantforce may be required to overcome the friction and inertia of thevarious components of the medical device in order to achieve movement ofthe expandable member. Thus, any reduction or minimization of points ofcontact between the guide and expandable member is advantageous as thefrictional forces generated during the relative movement will in turn beminimized, thereby reducing the amount of force required by the supportassembly, or manual operator, to establish relative movement. As theproximal components of medical device are often polymeric and nottorsionally rigid, undue friction on the expandable member can lead totorsional loading and unloading of the proximal members. This leads toinconsistent rotation of the medical device, which in turns leads tonon-uniform coating. Additionally, the presence of undue frictionalforces is undesired in that if the expandable member were to beaccidentally released from the guide, any coating applied could beundesirably smeared or discharged from the expandable member due to thereactionary force of the expandable member.

If desired, a protective sheath can be provided to protect the coatingduring shipping and storage and/or during delivery of the coatedexpandable member through the body lumen. A variety of sheaths areknown, including removable sheaths or balloon covers, retractablesheaths to be withdrawn prior to deployment of the balloon, and elasticsheaths that conform to the balloon upon expansion. Such elastic sheathscan be porous or include apertures along a portion thereof. Inoperation, the inflation of the expandable member causes the sheath toexpand for release of the coating and/or therapeutic agent through theporous wall or apertures to the tissue of the arterial wall. Forexample, see U.S. Pat. No. 5,370,614 to Amundson, the disclosure ofwhich is incorporated by reference in its entirety.

In accordance with in the disclosed subject matter, an endoprosthesis,e.g. stent, can be mounted on the expandable member. The type of stentthat can be used includes, but is not limited to, bare metal stent, drugeluting stent, bioabsorbable stent, balloon-expandable stent,self-expanding stent, prohealing stent, and self-expanding vulnerableplaque implant. The expandable member can be coated independently of thestent or in conjunction with the stent coating process. The stentcoating can contain the same or different therapeutic agents from thecatheter or expandable member. However, the particular coating on thecatheter or expandable member has distinct release kinetics from thetherapeutic coating on the stent. The coating applied to the expandablemember can be allowed to dry prior to placement of the stent thereon.

Alternatively, the coating could not be allowed to dry or cure past a“tacky” state before the stent is positioned and/or crimped onto it.This would enable the adhesion of the coating on the expandable memberto the inside of the prosthesis. This process increases the retention ofthe prosthesis onto the expandable member (acting as a prosthesisretention enhancer) thus reducing the chance that the stent will move onthe expandable member during the torturous delivery through the vascularlumen

While the disclosed subject matter is described herein in terms ofcertain embodiments, those skilled in the art will recognize thatvarious modifications and improvements can be made to the disclosedsubject matter without departing from the scope thereof. Moreover,although individual features of one embodiment of the disclosed subjectmatter can be discussed herein or shown in the drawings of the oneembodiment and not in other embodiments, it should be apparent thatindividual features of one embodiment can be combined with one or morefeatures of another embodiment or features from a plurality ofembodiments.

In addition to the specific embodiments claimed below, the disclosedsubject matter is also directed to other embodiments having any otherpossible combination of the dependent features claimed below and thosedisclosed above. As such, the particular features presented in thedependent claims and disclosed above can be combined with each other inother manners within the scope of the disclosed subject matter such thatthe disclosed subject matter should be recognized as also specificallydirected to other embodiments having any other possible combinations.Thus, the foregoing description of specific embodiments of the disclosedsubject matter has been presented for purposes of illustration anddescription. It is not intended to be exhaustive or to limit thedisclosed subject matter to those embodiments disclosed.

It will be apparent to those skilled in the art that variousmodifications and variations can be made in the method and system of thedisclosed subject matter without departing from the spirit or scope ofthe disclosed subject matter. Thus, it is intended that the disclosedsubject matter include modifications and variations that are within thescope of the appended claims and their equivalents.

1. A method of coating an expandable member of a medical device,comprising: providing an applicator in fluid communication with a fluidsource, the applicator having at least one outlet for applying fluidtherefrom; positioning the applicator proximate a surface of anexpandable member; establishing relative movement between the at leastone outlet and the surface of the expandable member along a coatingpath; maintaining a substantially fixed distance between the at leastone outlet and the surface of the expandable member during relativemovement therebetween; and applying fluid from the at least one outletto form a coating of fluid on the surface of the expandable member alongthe coating path.
 2. The method of claim 1, wherein maintaining thesubstantially fixed distance includes constraining displacement of theexpandable member during relative movement between the at least oneoutlet and the surface of the expandable member.
 3. The method of claim2, wherein constraining displacement includes providing a guide toconstrain displacement of the expandable member in at least onedirection during relative movement between the at least one outlet andthe surface of the expandable member.
 4. The method of claim 3, whereinthe guide includes at least one constraining member having at least onediscrete location of contact with the surface of the expandable member.5. The method of claim 3, wherein the guide includes at least twoconstraining members contacting generally opposing sides of theexpandable member.
 6. The method of claim 3, wherein the guide is agenerally U-shaped member having three discrete locations of contactwith the surface of the expandable member.
 7. The method of claim 3,wherein the guide substantially surrounds a perimeter of the expandablemember.
 8. The method of claim 2, wherein the amount of constrainment ofthe expandable member varies along a length of the expandable member. 9.The method of claim 8, wherein the amount of constrainment of theexpandable member increases along a length of the expandable member. 10.The method of claim 1, further comprising at least partially expandingthe expandable member prior to dispensing fluid to the surface of theexpandable member.
 11. The method of claim 1, wherein the guide is madeof polyethylene, polypropylene, poly(tetrafluoroethylene), fluorinatedethylene propylene (FEP), poly(vinylidene fluoride),poly(tetrafluoroethylene-co-ethylene), PEEK, or nylon.
 12. A system forcoating an expandable member of a medical device, the system comprising:a support structure to support an expandable member of a medical device;an applicator in fluid communication with a fluid source, the applicatorhaving at least one outlet for applying fluid of the fluid sourcetherefrom, the dispenser positioned with the at least one outletproximate a surface of an expandable member supported by the supportstructure; a drive assembly to establish relative movement between theat least one outlet and the surface of the expandable member to applyfluid on the surface of the expandable member along a coating path; anda guide to maintain a substantially fixed distance between the at leastone outlet and the surface of the expandable member during relativemovement therebetween.
 13. The system of claim 12, wherein the guideconstrains displacement of the expandable member in at least onedirection during relative movement between the at least one outlet andthe surface of the expandable member.
 14. The system of claim 13,wherein the guide includes at least one constraining member arrangedwith at least one discrete location of contact with the surface of theexpandable member.
 15. The system of claim 13, wherein the guideincludes at least two constraining members contacting generally opposingsides of the expandable member.
 16. The system of claim 13, wherein theguide is a generally U-shaped member having three discrete locations ofcontact with the surface of the expandable member.
 17. The system ofclaim 13, wherein the guide substantially surrounds a perimeter of theexpandable member.
 18. The system of claim 13, wherein a plurality ofguides are configured to progressively vary the amount of displacementof the expandable member.
 19. The system of claim 18, wherein theplurality of guides are configured to progressively increase the amountof displacement of the expandable member.
 20. The system of claim 12,wherein the guide is made of polyethylene, polypropylene,poly(tetrafluoroethylene), fluorinated ethylene propylene (FEP),poly(vinylidene fluoride), poly(tetrafluoroethylene-co-ethylene), PEEK,or nylon.